Search Results (3,426)

Despite the significant advancements in treatment and prevention, the fight against cancer is ongoing worldwide. This study evaluated the pharmacological properties and anticancer activity of Afzelia quanzensis bark, traditionally used by the indigenous communities of KwaZulu Natal and Eastern Cape Provinces of South Africa to treat cancer and related illnesses. Phytochemical screening, high-performance liquid chromatography–diode array detection (HPLC-DAD), and Fourier-transform infrared spectroscopy (FTIR) analyses were carried out using established protocols. The antioxidant activity was assessed via the 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and nitric oxide radicals. The anticancer activity was evaluated using the MTT assay (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Phytochemical analysis revealed the presence of saponins, flavonoids, terpenoids, alkaloids, steroids, cardiac glycosides, and phlobatannins. The HPLC-DAD analysis detected seven distinctive peaks in the aqueous extract and three distinctive peaks in the methanolic extract. The FTIR spectra of the aqueous extract displayed characteristic peaks corresponding to O-H, C=O, C=C, and =C–H functional groups. Among the tested extracts, the methanol extract exhibited the strongest antioxidant activity, followed by the ethanolic extract, in both DPPH and nitric oxide. The methanol extract showed a higher cell proliferation inhibition against the DU-145 cancer cell line with the percentage of inhibition of 37.8%, followed by the aqueous extract with 36.3%. In contrast, limited activity was observed against PC-3, SK-UT-1, and AGS cell lines. The results demonstrated notable dose-dependent antioxidant and antiproliferative activities supporting the ethnomedicinal use of Afzelia quanzensis bark in cancer management. These findings warrant further investigation into its bioactive constituents and mechanisms of action. Full article

Objectives: Diabetes Mellitus involves demanding challenges that interfere with family functioning and routines. In turn, family and social context impacts individual glycemic control. This study aims to identify this recursive interplay, the mutual influences of family systems and diabetes management. Design: Data was collected through a cross-sectional design comparing patients, aged 22–55, with and without metabolic control. Methods: Participants filled out a set of self-report measures of sociodemographic, clinical and family systems assessment. Patients (91) were also invited to describe their perception about disease management interference regarding family functioning. We first examined the extent to which family variables grouped dataset to determine if there were similarities and dissimilarities that fit with our initial diabetic groups’ classification. Results: Cluster analysis results identify a two-cluster solution validating initial classification of two groups of patients: 49 with metabolic control (MC) and 42 without metabolic control (NoMC). Independent sample tests suggested statistically significant differences between groups in family subscales- family difficulties and family communication (p < 0.05). Binary logistic regression shed light on predictors of explained variance to no metabolic control, in four models: Sociodemographic, Clinical data, SCORE-15/Congruence Scale and Eating Behavior. Furthermore, groups differ on family support, level and sources of family conflict caused by diabetes management issues. Considering only patients who co-habit with a partner for more than one year (N = 44), NoMC patients score lower on marital functioning in all categories (p < 0.05). Discussion: Family-Chronic illness interaction plays a significant role in a patient’s adherence to treatment. This study highlights the Standards of Medical Care for Diabetes, considering caregivers and family members on diabetes care. Full article

Background: Patients in Intensive Care Units (ICUs) often develop non-thyroidal illness syndrome. Potentially, thyroid hormones may be removed during continuous veno-venous hemodiafiltration (CVVHDF), as their molecular size is smaller than the filter pores’ cutoff. The study’s main aim was to assess whether the serum concentration of thyroid hormones changes over time during CVVHDF. Methods: This was a prospective observational trial that included 30 patients treated in an ICU. All patients developed acute kidney injury (AKI) and had clinical indications for implementation of CVVHDF. Blood samples were collected before initiation of CVVHDF and at 1, 2, 3, 6, 9 and 12 days after. The last sample was collected three days after CVVHDF withdrawal. Thyroid function was evaluated by determining the serum concentration of TSH, thyrotropin-releasing hormone (TRH), free triiodothyronine (fT₃), free thyroxine (fT₄), total triiodothyronine (tT₃), total thyroxine (tT₄) and reverse triiodothyronine (rT₃). We additionally calculated the total activity of peripheral deiodinases (G_D) using a mathematical model. Results: TRH and TSH levels remained mostly within normal ranges. fT4 and tT4 were in normal range or slightly below. In contrast, fT3 and tT3 were undetectably low in most patients throughout. Reverse T3 levels remained within normal limits. There were no statistically significant changes in any thyroid hormone levels over the CVVHDF treatment period. The calculated peripheral G_D activity was lower than normal, but importantly, it did not change significantly over time. Conclusions: Thyroid hormones are not lost due to hemodiafiltration. Decreased deiodinases activity is responsible for alterations in serum concentrations of thyroid hormones in patients during CVVHDF. Full article

Foodborne illness caused by bacterial pathogens is a global health concern and results in millions of infections annually. Therefore, food products typically undergo several processing stages, including sanitation steps, before being distributed in an attempt to remove pathogens. However, many sanitation methods have compounding effects on the color, texture, flavor, and nutritional quality of the product or do not effectively reduce the pathogens that food can be exposed to. Some bacterial pathogens particularly possess traits and tactics that make them even more difficult to mitigate such as biofilm formation. Non-thermal plasma sanitation techniques, including plasma-treated water (PTW), have proven to be promising methods that significantly reduce pathogenic bacteria that food is exposed to. Published work reveals that PTW can effectively mitigate both gram-positive and gram-negative bacterial biofilms. This study presents a novel analysis of the differences in antimicrobial effects of PTW treatment between biofilm-forming gram-positive bacteria, commonly associated with foodborne illness, that are sporulating (Bacillus cereus) and non-sporulating (Listeria monocytogenes). After treatment with PTW, the results suggest the following hypotheses: (1) that the non-sporulating species experiences less membrane damage but a greater reduction in metabolic activity, leading to a possible viable but non-culturable (VBNC) state, and (2) that the sporulating species undergoes spore formation, which may subsequently convert into vegetative cells over time. PTW treatment on gram-positive bacterial biofilms that persist in food processing environments proves to be effective in reducing the proliferating abilities of the bacteria. However, the variance in PTW’s effects on metabolic activity and cell vitality between sporulating and non-sporulating species suggest that other survival tactics might be induced. This analysis further informs the application of PTW in food processing as an effective sanitation method. Full article

Ceftazidime–avibactam (CAZ-AVI) is a second-generation intravenous β-lactam/β-lactamase inhibitor combination. In recent years, substantial evidence has emerged regarding the efficacy and safety of CAZ-AVI. However, data on its use in critically ill patients remain limited. Background/Objectives: This multicenter, retrospective, observational cohort study was conducted across four Intensive Care Units (ICUs) in three hospitals in the Marche region of Italy. The primary objective was to evaluate the 30-day clinical outcomes and identify risk factors associated with 30-day clinical failure—defined as death, microbiological recurrence, or persistence within 30 days after discontinuation of therapy—in critically ill patients treated with CAZ-AVI. Methods: The study included all adult critically ill patients admitted to the participating ICUs between January 2020 and September 2023 who received CAZ-AVI for at least 72 h for the treatment of a confirmed or suspected Gram-negative bacterial (GNB) infection. Results: Among the 161 patients included in the study, CAZ-AVI treatment resulted in a positive clinical outcome (i.e., clinical improvement and 30-day survival) in 58% of cases (n = 93/161), while the overall mortality rate was 24% (n = 38/161). Relapse or persistent infection occurred in a substantial proportion of patients (25%, n = 41/161). Notably, acquired resistance to CAZ-AVI was observed in 26% of these cases, likely due to suboptimal use of the drug in relation to its pharmacokinetic/pharmacodynamic (PK/PD) properties in critically ill patients. Furthermore, treatment failure was more frequent among immunosuppressed individuals, particularly liver transplant recipients. Conclusions: This study demonstrates that the mortality rate among ICU patients treated with this novel antimicrobial combination is consistent with findings from other studies involving heterogeneous populations. However, the rapid emergence of resistance underscores the need for vigilant surveillance and the implementation of robust antimicrobial stewardship strategies. Full article

Background: Accumulating evidence indicates that SARS-CoV-2 infection results in long-term multiorgan complications, with the kidney being a primary target. This study aimed to characterize the long-term transcriptomic changes in the kidney following coronavirus infection using a murine model of MHV-1-induced SARS-like illness and to evaluate the therapeutic efficacy of SPIKENET (SPK). Methods: A/J mice were infected with MHV-1. Renal tissues were collected and subjected to immunofluorescence analysis and Next Generation RNA Sequencing to identify differentially expressed genes associated with acute and chronic infection. Bioinformatic analyses, including PCA, volcano plots, and GO/KEGG pathway enrichment, were performed. A separate cohort received SPK treatment, and comparative transcriptomic profiling was conducted. Gene expression profile was further confirmed using real-time PCR. Results: Acute infection showed the upregulation of genes involved in inflammation and fibrosis. Long-term MHV-1 infection led to the sustained upregulation of genes involved in muscle regeneration, cytoskeletal remodeling, and fibrotic responses. Notably, both expression and variability of SLC22 and SLC22A8, key proximal tubule transporters, were reduced, suggesting a loss of segment-specific identity. Further, SLC12A1, a critical regulator of sodium reabsorption and blood pressure, was downregulated and is associated with the onset of polyuria and hydronephrosis. SLC transporters exhibited expression patterns consistent with tubular dysfunction and inflammation. These findings suggest aberrant activation of myogenic pathways and structural proteins in renal tissues, consistent with a pro-fibrotic phenotype. In contrast, SPK treatment reversed the expression of most genes, thereby restoring the gene profiles to those observed in control mice. Conclusions: MHV-1-induced long COVID is associated with persistent transcriptional reprogramming in the kidney, indicative of chronic inflammation, cytoskeletal dysregulation, and fibrogenesis. SPK demonstrates robust therapeutic potential by normalizing these molecular signatures and preventing long-term renal damage. These findings underscore the relevance of the MHV-1 model and support further investigation of SPK as a candidate therapy for COVID-19-associated renal sequelae. Full article

If God cares and is present, can God use pain and suffering in my life? Absolutely. Does this mean that God planned, ordained, or designed the pain (or cancer) to be instrumental in my life for some sort of higher spiritual purpose? If so, why? Why does God allow cancer to invade and interrupt one’s life? There are no theologically sound or definitive answers to these questions. Although asking such questions is basic to our humanity, as we will observe in various passages of Scripture, the answers will always remain elusive. Instead of seeking to answer the question “why?”, I will suggest two areas for theological and pastoral reflection with respect to those facing cancer: humility and hope. Enduring cancer, from diagnosis through treatment, requires humility in mind and body before our Creator and before our caregivers. Cancer also provides an opportunity for Christians to embed themselves in the hope of resurrection and new creation. Resurrection hope is also not reduced to hope beyond death but hope that is manifested now through embodied resurrection “signs” and actions of human sacrificial love, both received and practiced by the patient undergoing illness and by the patient’s caregivers, family, and friends. Full article

Background/Objective: The COVID-19 pandemic profoundly transformed social life worldwide, indiscriminately affecting individuals across all age groups. Children have not been exempted from the risk of severe illness and death caused by COVID-19. Objective: This paper sought to describe the clinical findings, laboratory and imaging results, and hospital care provided for severe and critical cases of COVID-19 in unvaccinated children, with or without severe asthma, hospitalized in a public referral service for COVID-19 treatment in the Brazilian state of Pernambuco. Methods: This was a case series study of severe and critical COVID-19 in hospitalized, unvaccinated children, with or without severe asthma, conducted in a public referral hospital between March 2020 and June 2021. Results: The case series included 80 children, aged from 1 month to 11 years, with the highest frequency among those under 2 years old (58.8%) and a predominance of males (65%). Respiratory diseases, including severe asthma, were present in 73.8% of the cases. Pediatric multisystem inflammatory syndrome occurred in 15% of the children, some of whom presented with cardiac involvement. Oxygen therapy was required in 65% of the cases, mechanical ventilation in 15%, and 33.7% of the children required intensive care in a pediatric intensive care unit. Pulmonary infiltrates and ground-glass opacities were common findings on chest X-rays and CT scans; inflammatory markers were elevated, and the most commonly used medications were antibiotics, bronchodilators, and corticosteroids. Conclusions: This case series has identified key characteristics of children with severe and critical COVID-19 during a period when vaccines were not yet available in Brazil for the study age group. However, the persistence of low vaccination coverage, largely due to parental vaccine hesitancy, continues to leave children vulnerable to potentially severe illness from COVID-19. These findings may inform the development of public health emergency contingency plans, as well as clinical protocols and care pathways, which can guide decision-making in pediatric care and ensure appropriate clinical management, ultimately improving the quality of care provided. Full article

Background: Pain is a problem faced by critically ill surgical patients and has a major impact on their outcomes. Pain assessment is therefore essential for effective pain management, with a combination of pharmacological and non-pharmacological treatment. Clinical supervision, supported by models such as SafeCare, can improve professional development, safety and the quality of care in intensive care units. Objectives: This study aimed to: (1) assess current pain assessment practices in a polyvalent Intensive Care Unit (ICU) in the Porto district; (2) identify nurses’ training needs regarding the Clinical Supervision-Sensitive Indicator—Pain; and (3) evaluate the impact of clinical supervision sessions on pain assessment practices. Methods: A quantitative, quasi-experimental, cross-sectional study with a pre- and post-intervention design was conducted. Based on the SafeCare model, it included a situational diagnosis, 6 clinical supervision sessions (February 2023), and outcome evaluation via nursing record audits (November 2022 and May 2023) in 31 total critical ill patients. Pain was assessed using standardised tools, in line with institutional protocols. Data was analysed using Software Statistical Package for the Social Sciences v25.0. Results: Pain was highly prevalent in the first 24 h, decreasing during hospitalisation. Generalised acute abdominal pain predominated, with mild to moderate intensity, and was exacerbated by wound care and mobilisation/positioning. Pain management combined pharmacological and non-pharmacological treatment. There was an improvement in all the parameters of the pain indicator post-intervention. Conclusions: Despite routine assessments, gaps remained in reassessing pain post-analgesia and during invasive procedures. Targeted clinical supervision and ongoing training proved effective in improving compliance with protocols and supporting safer, more consistent pain management. Full article

Background: Studies have demonstrated a positive correlation between high body mass index (BMI) and an increased risk of Clostridioides difficile infection (CDI), independent of antibiotic usage or healthcare exposures. Aim: To compare the outcomes of obese (BMI ≥ 30 kg/m²) and non-obese (BMI < 30 kg/m²) hospitalized patients with CDI. Methods: This retrospective cohort study included patients with CDI hospitalized in Beilinson hospital between January 2013 and January 2020. The primary outcome was 90-day all-cause mortality. Secondary outcomes included 30-day mortality, colectomy, intensive care unit (ICU) admission and length of hospital stay (LOS). Multivariate analysis was performed to identify the risk factors independently associated with 90-day mortality. Results: The study included 889 patients: 131 (15%) obese and 758 (85%) non-obese. The obese group was younger (median age 65 years vs. 73 years (p < 0.01)) and with a higher rate of diabetes mellitus (57/131 (44%) vs. 180/758 (24%) (p < 0.01)). The 90-day mortality was lower in the obese group: 19/131 (15%) vs. 170/752 (23%) (p = 0.04). The 30-day mortality was 8/131 (6%) vs. 96/757 (13%) (p = 0.03). ICU admission was 9/131 (7%) vs. 23/758 (3%) (p = 0.03), and median LOS was 19 vs. 12 days (p < 0.01) in obese and non-obese groups, respectively. In the multivariable analysis, after adjustment for age, Charlson’s comorbidity index ≥3, assistance in activities of daily living, treatment with proton pump inhibitors and severity of illness, obesity was not a significant risk factor for 90-day mortality (OR = 0.65, 95% CI: 0.38–1.01; p = 0.1). Conclusions: In this study, obesity was not significantly associated with 90-day mortality after adjustment for other risk factors; however, ICU admission was higher and LOS longer in this group. Full article

Background: Comorbid personality disorders (PDs) in patients with anorexia nervosa (AN) are associated with increased psychopathology, higher suicide risk, and poorer treatment response and outcomes. This study aimed to examine associations between gray matter (GM) volume and PDs in female adolescents with AN before and after short-term psychotherapeutic and nutritional therapy. Methods: Eighteen female adolescents with acute AN, mean age 15.9 years, underwent 3T magnetic resonance imaging before and after weight restoration. The average interval between scans was 2.6 months. Structural brain changes were analyzed using voxel-based morphometry. PDs were assessed using the Structured Clinical Interview for DSM-IV Axis II Disorders (SCID II) and the Assessment of Identity Development Questionnaire. Results: SCID-II total scores showed significant positive associations with GM volume in the mid-cingulate cortex at both time points and in the left superior parietal–occipital lobule at baseline. The histrionic subscale correlated with GM volume in the thalamus bilaterally and the left superior parietal–occipital lobule in both assessments, as well as with the mid-cingulate cortex at follow-up. Borderline and antisocial subscales were associated with GM volume in the thalamus bilaterally at baseline and in the right mid-cingulate cortex at follow-up. Conclusions: PDs in female adolescent patients with AN may be specifically related to GM alterations in the thalamus, cingulate, and parieto-occipital regions, which are present during acute illness and persist after weight restoration therapy. Full article

Background: Nigella sativa, known as black cumin, is traditionally used to treat various illnesses. Objective: The current study aims to investigate the potential hepatoprotective and nephroprotective effect of black cumin fractions via per os route in CCl₄-intoxicated Wistar rats. This study used a computational approach to assess the interaction of bioactive compounds with key proteins (CYP P450 3E1, TNF-α, and Cox-2). Methods:Wistar rats were treated with CCl₄ to induce liver injury and with different Nigella sativa fractions (250 mg/Kg) or Sylimarin (50 mg/Kg). Liver and kidney functions were assessed through biochemical markers, hepatic glycogen, malondialdehyde levels, molecular docking, and ADMET analysis to evaluate drug-likeliness. Results: The results revealed that intoxication with CCl₄ induced an elevation in different liver and kidney biochemical parameters such as (ALT, AST, creatinine, urea...) indicating kidney and hepatic toxicity. However, treatment with different Nigella sativa fractions showed a significant improvement in animal body weight and significant amelioration of biochemical markers indicating a protective potential of these fractions against CCl₄-induced intoxication. Furthermore, the molecular docking approach demonstrated high binding affinity with the target proteins. Conclusions: These current findings shed light on the therapeutic potential of Nigella sativa fractions as a promising protective agent of the liver and kidney against CCl₄ intoxication. Full article

The increasing demand for fresh fruits and vegetables has been accompanied by a rise in foodborne illness outbreaks linked to fresh produce. Traditional antimicrobial washing treatments, such as chlorine and peroxyacetic acid, have limitations in efficacy and pose environmental and worker health concerns. This study evaluated the effectiveness of organic acids (citric, malic, and lactic acid) and power ultrasound, individually and in combination, for the reduction in Salmonella enterica and Listeria monocytogenes on four fresh produce types: romaine lettuce, cucumber, tomato, and strawberry. Produce samples were inoculated with bacterial cocktails at 8–9 log CFU/unit and treated with organic acids at 2 or 5% for 2 or 5 min, with or without power ultrasound (40 kHz). Results showed that pathogen reductions varied based on the produce matrix with smoother surfaces such as tomato, exhibiting greater reductions than rougher surfaces (e.g., romaine lettuce and strawberry). Lactic and malic acids were the most effective treatments, with 5% lactic acid achieving a reduction of >5 log CFU/unit for S. enterica and 4.53 ± 0.71 log CFU/unit for L. monocytogenes on tomatoes. The combination of organic acids and power ultrasound demonstrated synergistic effects, further enhancing pathogen reduction by <1.87 log CFU/unit. For example, S. enterica on cucumbers was reduced by an additional 1.87 log CFU/unit when treated with 2% malic acid and power ultrasound for 2 min compared to malic acid alone. Similarly, L. monocytogenes on strawberries was further reduced by 1.84 log CFU/unit when treated with 5% malic acid and power ultrasound for 2 min. These findings suggest that organic acids, particularly malic and lactic acids, combined with power ultrasound, may serve as an effective hurdle technology for enhancing the microbial safety of fresh produce. Future research can include validating these treatments in an industrial processing environment. Full article

Objectives: To assess the role of a real-time therapeutic drug monitoring (TDM)-guided expert clinical pharmacological advice (ECPA) program of isavuconazole in preventing under- or overexposure with the intent of improving efficacy and safety outcomes in the critically ill patients. Methods: This retrospective study included critical patients receiving intravenous isavuconazole for prophylaxis or treatment of invasive fungal infections (IFI) and undergoing at least one TDM-guided ECPA in the period 1 March 2021–31 March 2025. Desired isavuconazole exposure was defined as trough concentrations (C_min) of 1.0–5.1 mg/L. Efficacy outcome was assessed by means of bronchoalveolar (BAL) galactomannan (GM) index, breakthrough IFI, and 30-day mortality rate, whereas safety was assessed by means of hepatic test disturbances (HTD). Univariate analysis was carried out for assessing potential variables associated with isavuconazole under- or overexposure and for comparing features of solid organ transplant (SOT) recipients vs. non-SOT patients. Proportions of isavuconazole C_min underexposure, desired exposure, and overexposure were assessed at different timepoints from starting therapy. Trends over time of HTD in relation to isavuconazole exposure were assessed separately in patients having HTD or not at baseline. Results: Overall, 32 critical patients were included. A total of 166 TDM-guided ECPAs were provided. Median (IQR) average isavuconazole C_min was 3.5 mg/L (2.1–4.6 mg/L). Proportions of ECPAs with isavuconazole C_min under- and overexposure were 4.2% (7/166) and 16.3% (27/166), respectively. Patients experiencing underexposure had higher body mass index (30.1 vs. 25.5 kg/m²; p < 0.001). Trends of isavuconazole C_min under- and overexposure changed over time, significantly decreasing the former (10.5% <7 days vs. 4.3% 7–28 days vs. 0.0% >28 days; p < 0.001) and increasing the latter (5.3% <7 days vs. 12.8% 7–28 days vs. 29.3% >28 days; p < 0.001). HTD occurred in 15/32 patients, most of whom (10/15) were affected just at baseline. Patients with transient or persistent overexposure trended toward a higher risk of HTD compared to those without (33.3% vs. 8.3%; p = 0.11). Conclusions: A real-time TDM-guided approach could be a valuable tool for optimizing isavuconazole exposure, especially whenever dealing with obese patients or with prolonged treatment. Full article

Introduction: The World Health Organization has declared carbapenem-resistant organisms a research and development priority. Although ceftazidime–avibactam was approved around a decade ago, there is still a lack of prospective data on the treatment of resistant pathogens with this agent. Methods: We conducted a prospective, observational, single-center, investigator-initiated study of patients treated with ceftazidime–avibactam for infections caused by carbapenem-resistant organisms. The primary outcome was clinical cure 14 days after the initiation of ceftazidime-avibactam treatment. Secondary outcomes, which were assessed on day 30, included microbiological failure, development of resistance, all-cause mortality, and length of stay in the intensive care unit. Results: A total of 50 patients were included in the study. At baseline, the median Charlson Comorbidity Index and Sequential Organ Failure Assessment Score were 5.5 and 7. Approximately three-quarters of the patients were treated in an intensive care unit and had undergone mechanical ventilation within the previous 7 days prior to the commencement of ceftazidime–avibactam treatment. Half of the patients were diagnosed with nosocomial pneumonia. Most infections were caused by Pseudomonas aeruginosa (48%) and Klebsiella pneumonia (28%). Clinical cure at day 14 was achieved in 59% of patients. Four deaths (9%) and two cases of microbiological failure (4%) were observed. The median length of stay in the intensive care unit was 14 days. There was no emergence of resistance to ceftazidime–avibactam. Discussion: Our study contributes to the growing body of evidence supporting the effectiveness of ceftazidime–avibactam in treating infections caused by carbapenem-resistant organisms. In this cohort of critically ill patients, our results in terms of both clinical success and survival are in the upper range compared to those from mainly retrospective and some prospective studies. Although the benefits of ceftazidime–avibactam have been demonstrated in this and other studies, it must be prescribed cautiously to ensure it remains effective. Full article